On episode #246 of the science show This Week in Virology, Vincent, Alan, Rich, and Kathy discuss the huge Pandoravirus, virologists planning H7N9 gain of function experiments, and limited access to the HeLa cell genome sequence.

There have been 131 confirmed human infections with avian influenza H7N9 virus in China, but so far there is little evidence for human to human transmission. Three out of four patients report exposure to animals, ‘mostly chickens‘, suggesting that most of the infections are zoonoses. Whether or not the virus will evolve to transmit among humans is anyone’s guess. Meanwhile it has been found that one of the H7N9 virus isolates from Shanghai can transmit by aerosol among ferrets, albeit inefficiently.

Ferrets were inoculated intranasally with influenza A/Shanghai/02/2013 virus or A/California/07/2009, the 2009 pandemic H1N1 virus. One to two days later the ferrets developed fever, sneezing, coughing, and nasal discharge; both viruses induced similar clinical signs. Virus was shed in nasal secretions for 7 days. Six infected ferrets were then divided among three separate cages, and each group was housed with a naive ferret, and a second uninfected animal was placed in an adjacent cage. Airflow was controlled so that air flowed from the cage of infected animals towards the cage of naive animals. Transmission of infection was measured by observing clinical signs, and measuring virus shedding in nasal secretions and hemagglutination-inhibition antibodies in serum.

Of the three ferrets housed in the same cage with H7N9 virius-infected animals, all three had signs of infection (sneeze, cough, nasal discharge), shed virus in nasal secretions, and developed anti-HA antibodies. All three ferrets in neighboring cages developed signs of infection, but only one shed virus in nasal secretions, and two of three seroconverted. From these data the authors conclude that H7N9 virus is ‘efficiently transmitted between ferrets by direct contact, but less efficiently by airborne exposure’. In contrast, transmission of H1N1 virus to naive ferrets by contact or aerosol was efficient (3/3 animals in both cases).

The authors also found that pigs could be infected intranasally with A/Shanghai/02/2013 virus: the animals shed virus in nasal secretions and developed clinical symptoms. However the infected pigs transmitted infection inefficiently to other pigs by contact or aerosol, or to ferrets by aerosol.

The authors’ equivocal conclusion that “Under appropriate conditions human to human transmission of the H7N9 virus may be possible” could have been reached even before these experiments were done. Their results provide no information on whether the virus can undergo human to human transmission because animal models are not definitive predictors of what might occur in humans. I disagree with the authors’ statement on page 5, “Efficient transmission of influenza viruses in ferrets is considered as a predictor of human to human transmissibility’. While many influenza virus strains that transmit among humans by aerosol also do so in ferrets, this does not mean that human transmission of a novel virus can be predicted by animal experiments.

Infection of ferrets with A/Shanghai/02/2013 or or A/California/07/2009 virus results in mild disease with no mortality. In contrast, 32 humans infected with H7N9 virus have died, and many humans have died after H1N1 infection. These findings further emphasize the differences in influenza virus pathogenesis in ferrets and humans.

On episode #230 of the science show This Week in Virology, Vincent, Rich, Alan and Kathy review H7N9 infections in China, the debate over patenting genes, and receptor-binding by ferret-transmissible avian H5 influenza virus.

We diagnosed avian influenza A H7N9 in all four patients (who were epidemiologically unlinked), two of whom died and two of whom were recovering at the time of writing. All patients had histories of occupational or wet market exposure to poultry. The genes of the H7N9 virus in patient 3’s isolate were phylogenetically clustered with those of the epidemiologically linked wet market chicken H7N9 isolate. These findings suggest sporadic poultry-to-person transmission.

The four patients had occupational contact with poultry: one was a chef, one slaughtered and cooked live market poultry, and two bought live market poultry. Each had contact with poultry 3-8 days before onset of disease, and all were positive for influenza H7N9 virus by polymerase chain reaction of sputum or throat swab samples (virus was cultured from three of the four patients). Two of five pigeons and four of 20 chickens from two different wet markets were also positive for influenza H7N9 virus. Sequence analysis of virus recovered from patient 3 revealed that the HA and NA genes are nearly identical with those of two viruses isolated from epidemiologically linked chickens (1673 of 1683 bases for HA, 1394 of 1398 bases for NA).

While these H7N9 infections might have been acquired from poultry, the origin of other infections in different areas of China (>100) is unclear. According to the Ministry of Agriculture, as of 26 April 2013, only 46 of the 68,060 samples collected from poultry markets, habitats, farms and slaughterhouses across the country have tested positive for H7N9 virus, and none of these positive samples have been from poultry farms.

The World Health Organization has been publishing weekly reports on the avian influenza A(H7N9) outbreak which include the geographical location of each case, the cumulative number of cases, and the epidemiological curve. Go to this page at the WHO website for an archive of the weekly reports (there you will also find other useful information on the H7N9 outbreak). Images for report #3 of 24 April 2013 are reproduced below. Click each image for a larger view.

In the late afternoon of April 24, 2013, the Central Epidemic Command Center (CECC) confirmed the first imported case of H7N9 avian influenza in a 53-year-old male Taiwanese citizen who worked in Suzhou, Jiangsu Province, China prior to illness onset. He developed his illness three days after returning to Taiwan. Infection with avian influenza A (H7N9) was confirmed on April 24, 2013. The patient is currently in a severe condition and being treated in a negative-pressure isolation room.

It’s not clear how the patient acquired the infection in China; he had no contact with birds or poultry and did not eat undercooked poultry or eggs.

The patient has had contact with 139 others, and all but 3 have used the appropriate personal protective equipment to prevent infection.

There is still no evidence for human-to-human transmission of avian influenza H7N9 virus in China. If this trend continues in Taiwan there should be no spread of the virus to others.

As long as people are allowed to travel from China, this probably won’t be the only imported case.